Coupling and transduction of energy is a pervasive theme in biology, and is indeed the dominant purpose of many proteins that perform energy conversion in respiration chemical transformation in catalysis, and recognition and signaling in activation and regulation. Our project brings together investigators who will use recent innovative developments in analysis, synthesis and theoretical skills to study this central principle of proteins. Goal 1 is to give a quantitative description of the environment of redox cofactors (especially hemes), with the view of describing energy transduction and the effect of electric field perturbations on the physical and chemical properties of heroes and related cofactors. This goal also includes a quantitative description of the dynamical qualities of proteins and factors involved in protein stability. In Goal 2 the aim is to develop predictive descriptions of the cofactor and protein spectra, reactivities and structures, with an iterative cycle of design, synthesis, measurement, analysis and simulation/model development. The proposed program consists of six interlocking projects with a common intellectual thread of understanding the basic forces that determine protein structure and reactivity, using coupling and energy transduction both as an overarching explanatory principle, and as an investigative tool. The research makes use of one-of-a-kind materials, including de novo designed peptides and protein maquettes with given structure, isotopically labeled material and modified heroes, and alter selected redox cofactors that are designed and synthesized by DeGrado, Dutton, Therien and Vanderkooi to address specific issues of protein energy transduction. Fundamental aspects of vibrational energy transfer in proteins will be examined by Hochstrasser, in a series of experiments that includes collaboration with DeGrado, Vanderkooi, Therien and Sharp. Protein relaxation around charge separated states is a theme of Therien's proposal, in collaboration with Hochstrasser and DeGrado, and directly related to the effects of distribution of charges and the propagation and suppression of electric fields being examined by Vanderkooi and Dutton. Investigators share with the program computational skills including electric field, dynamics and quantum mechanics calculations carried out by Sharp.